Is USP3 p.Pro360Thr (c.1078C>A) pathogenic?

USP3 p.Pro360Thr (c.1078C>A) is classified Benign in USP3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-09-19). AlphaMissense: likely benign (0.0988); Common (popmax 8.4%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about USP3 p.Pro360Thr (c.1078C>A)?

AlphaMissense predicts likely benign (score 0.0988) — an in-silico prediction, not a clinical call.

USP3 p.Pro360Thr

Q: How common is USP3 p.Pro360Thr (c.1078C>A) in the general population?

USP3 p.Pro360Thr (c.1078C>A) is common (popmax 8.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1078C>A · rs34776764 · VCV710052

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0988 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.4%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0988	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -6.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 86 kb · p 7.7e-10 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.4% African / African-American · 6,240/74,302 alleles

Filtering AF 8.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.15%

Overall 0.442% 7,096/1,603,716 alleles · common exomes 3,409/1,451,528 · genomes 3,687/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.4%	12
Admixed American	0.603%	166
Remaining individualsnot grpmax-eligible	0.543%	184
Middle Eastern	0.449%	223
South Asian	0.0271%	3,690
European (non-Finnish)	0.00986%	10,139

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: USP3
Protein: p.Pro360Thr
Coding: c.1078C>A
MANE Select: NM_006537
dbSNP: rs34776764
Type: single nucleotide variant
Location: chr15:63574385 (GRCh38)
Gene constraint: LOEUF 0.456 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.40
Residue 360: the usp domain; a UniProt-annotated variant site (in)

Full USP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

USP3 p.Ala306Glu Uncertain significance ★ ⚠ same type
USP3 p.Ala64Thr Uncertain significance ★ ⚠ same type
USP3 p.Arg204Gln Uncertain significance ★ same type
USP3 p.Arg204Trp Uncertain significance ★ ⚠ same type
USP3 p.Arg332Thr Uncertain significance ★ ⚠ same type
USP3 p.Arg33Leu Uncertain significance ★ ⚠ same type
USP3 p.Arg352Cys Uncertain significance ★ ⚠ same type
USP3 p.Arg365Gln Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/usp3-p-pro360thr (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown